{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:50:30Z","timestamp":1790171430695,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2019,8,15]],"date-time":"2019-08-15T00:00:00Z","timestamp":1565827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31670797"],"award-info":[{"award-number":["31670797"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lung tissues are frequently exposed to a hyperoxia environment, which leads to oxidative stress injuries. Hydrogen sulfide (H2S) is widely implicated in physiological and pathological processes and its antioxidant effect has attracted much attention. Therefore, in this study, we used hydrogen peroxide (H2O2) as an oxidative damage model to investigate the protective mechanism of H2S in lung injury. Cell death induced by H2O2 treatment could be significantly attenuated by the pre-treatment of H2S, resulting in a decrease in the Bax\/Bcl-2 ratio and the inhibition of caspase-3 activity in human lung epithelial cell line A549 cells. Additionally, the results showed that H2S decreased reactive oxygen species (ROS), as well as neutralized the damaging effects of H2O2 in mitochondria energy-producing and cell metabolism. Pre-treatment of H2S also decreased H2O2-induced suppression of endogenous H2S production enzymes, cystathionine-beta-synthase (CBS), cystathionine-gamma-lyase (CSE), and 3-mercapto-pyruvate sulfurtransferase (MPST). Furthermore, the administration of H2S attenuated [Ca2+] overload and endoplasmic reticulum (ER) stress through the mitogen-activated protein kinase (MAPK) signaling pathway. Therefore, H2S might be a potential therapeutic agent for reducing ROS and ER stress-associated apoptosis against H2O2-induced lung injury.<\/jats:p>","DOI":"10.3390\/ijms20163975","type":"journal-article","created":{"date-parts":[[2019,8,15]],"date-time":"2019-08-15T11:11:00Z","timestamp":1565867460000},"page":"3975","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Hydrogen Sulfide Attenuates Hydrogen Peroxide-Induced Injury in Human Lung Epithelial A549 Cells"],"prefix":"10.3390","volume":"20","author":[{"given":"Mingqi","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, College of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Cao","sequence":"additional","affiliation":[{"name":"Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, College of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Luan","sequence":"additional","affiliation":[{"name":"Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, College of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4025-2117","authenticated-orcid":false,"given":"Zhengqiang","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, College of Life Sciences, Jilin University, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1002\/biof.1061","article-title":"H2S: a \u201cdouble face\u201d molecule in health and disease","volume":"39","author":"Ascenzi","year":"2013","journal-title":"Biofactors"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1007\/s00204-018-2208-x","article-title":"Activation of autophagic flux and the Nrf2\/ARE signaling pathway by hydrogen sulfide protects against acrylonitrile-induced neurotoxicity in primary rat astrocytes","volume":"92","author":"Yang","year":"2018","journal-title":"Arch. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1089\/ars.2009.2938","article-title":"Hydrogen sulfide: the third gasotransmitter in biology and medicine","volume":"12","author":"Wang","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/978-3-319-18144-8_12","article-title":"Hydrogen Sulfide and Cancer","volume":"230","author":"Hellmich","year":"2015","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"12474","DOI":"10.1073\/pnas.1306241110","article-title":"Tumor-derived hydrogen sulfide, produced by cystathionine-beta-synthase, stimulates bioenergetics, cell proliferation, and angiogenesis in colon cancer","volume":"110","author":"Szabo","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1165\/rcmb.2015-0385OC","article-title":"Hydrogen Sulfide Is an Antiviral and Antiinflammatory Endogenous Gasotransmitter in the Airways. Role in Respiratory Syncytial Virus Infection","volume":"55","author":"Ivanciuc","year":"2016","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/nrd2425","article-title":"Hydrogen sulphide and its therapeutic potential","volume":"6","author":"Szabo","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s00726-010-0510-x","article-title":"Hydrogen sulfide: its production, release and functions","volume":"41","author":"Kimura","year":"2011","journal-title":"Amino Acids"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/1751-2980.12019","article-title":"Is NSAIDs-related gastrointestinal damage preventable?","volume":"14","author":"Gargallo","year":"2013","journal-title":"J. Dig. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.niox.2014.11.010","article-title":"H2S-releasing drugs: anti-inflammatory, cytoprotective and chemopreventative potential","volume":"46","author":"Gemici","year":"2015","journal-title":"Nitric Oxide"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1002\/cphy.c150028","article-title":"Lung Structure and the Intrinsic Challenges of Gas Exchange","volume":"6","author":"Hsia","year":"2016","journal-title":"Compr. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1745-6673-1-6","article-title":"Analysing the causes of chronic cough: relation to diesel exhaust, ozone, nitrogen oxides, sulphur oxides and other environmental factors","volume":"1","author":"Kraus","year":"2006","journal-title":"J. Occup. Med. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"123","DOI":"10.4187\/respcare.01963","article-title":"Hyperoxic acute lung injury","volume":"58","author":"Kallet","year":"2013","journal-title":"Respir. Care"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e00275-17","DOI":"10.1128\/JVI.00275-17","article-title":"Contribution of Human Lung Parenchyma and Leukocyte Influx to Oxidative Stress and Immune System-Mediated Pathology following Nipah Virus Infection","volume":"91","author":"Escaffre","year":"2017","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"H1453","DOI":"10.1152\/ajpheart.00554.2015","article-title":"Drug-induced mitochondrial dysfunction and cardiotoxicity","volume":"309","author":"Varga","year":"2015","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1971452","DOI":"10.1155\/2016\/1971452","article-title":"Oxidative Stress after Surgery on the Immature Heart","volume":"2016","author":"Fudulu","year":"2016","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1038\/onc.2016.357","article-title":"Phosphorylation of cofilin-1 by ERK confers HDAC inhibitor resistance in hepatocellular carcinoma cells via decreased ROS-mediated mitochondria injury","volume":"36","author":"Liao","year":"2017","journal-title":"Oncogene"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1152\/physrev.00026.2013","article-title":"Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release","volume":"94","author":"Zorov","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.canlet.2019.01.034","article-title":"Endoplasmic reticulum proteostasis control and gastric cancer","volume":"449","author":"Wang","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"170018","DOI":"10.1183\/16000617.0018-2017","article-title":"Endoplasmic reticulum stress in lung disease","volume":"26","author":"Marciniak","year":"2017","journal-title":"Eur. Respir. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s11882-017-0751-9","article-title":"Endoplasmic Reticulum Stress and Allergic Diseases","volume":"17","author":"Jeong","year":"2017","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.neuropharm.2017.11.016","article-title":"Crosstalk between endoplasmic reticulum stress and brain inflammation in Alzheimer\u2019s disease","volume":"136","author":"Santos","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s11883-017-0669-7","article-title":"Endoplasmic Reticulum Stress, NRF2 Signalling and Cardiovascular Diseases in a Nutshell","volume":"19","author":"Mozzini","year":"2017","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/978-3-319-48382-5_11","article-title":"Endoplasmic Reticulum Stress and Obesity","volume":"960","author":"Yilmaz","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1378\/chest.12-2133","article-title":"Protein misfolding and endoplasmic reticulum stress in chronic lung disease","volume":"143","author":"Wei","year":"2013","journal-title":"Chest"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/sj.mp.4000789","article-title":"Evidence that the activities of erythrocyte free radical scavenging enzymes and the products of lipid peroxidation are increased in different forms of schizophrenia","volume":"6","author":"Herken","year":"2001","journal-title":"Mol. Psychiatry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1164\/ajrccm.162.6.9912144","article-title":"Effect of free radical scavengers on diaphragmatic contractility in septic peritonitis","volume":"162","author":"Fujimura","year":"2000","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.mvr.2005.04.003","article-title":"Change in mitochondrial membrane potential is the key mechanism in early warm hepatic ischemia-reperfusion injury","volume":"70","author":"Sun","year":"2005","journal-title":"Microvasc. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/s41419-019-1492-6","article-title":"beta-Thujaplicin induces autophagic cell death, apoptosis, and cell cycle arrest through ROS-mediated Akt and p38\/ERK MAPK signaling in human hepatocellular carcinoma","volume":"10","author":"Zhang","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1152\/physrev.00017.2011","article-title":"Physiological implications of hydrogen sulfide: a whiff exploration that blossomed","volume":"92","author":"Wang","year":"2012","journal-title":"Physiol. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1089\/ars.2014.5901","article-title":"Anti-inflammatory and cytoprotective actions of hydrogen sulfide: translation to therapeutics","volume":"22","author":"Wallace","year":"2015","journal-title":"Antioxid Redox Signal."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.pupt.2014.06.001","article-title":"Airway and systemic oxidant-antioxidant dysregulation in asthma: a possible scenario of oxidants spill over from lung into blood","volume":"29","author":"Nadeem","year":"2014","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.freeradbiomed.2009.12.022","article-title":"Reactive oxygen species, cellular redox systems, and apoptosis","volume":"48","author":"Circu","year":"2010","journal-title":"Free Radic Biol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"10336","DOI":"10.1038\/srep10336","article-title":"Licochalcone A-induced human gastric cancer BGC-823 cells apoptosis by regulating ROS-mediated MAPKs and PI3K\/AKT signaling pathways","volume":"5","author":"Hao","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1126\/science.1072682","article-title":"Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases","volume":"298","author":"Johnson","year":"2002","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1161\/HYPERTENSIONAHA.109.130054","article-title":"Mitochondria and reactive oxygen species","volume":"53","author":"Addabbo","year":"2009","journal-title":"Hypertension"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1177\/0963689718779361","article-title":"Hydrogen Sulfide Protects Human Cardiac Fibroblasts Against H2O2-induced Injury Through Regulating Autophagy-Related Proteins","volume":"27","author":"Feng","year":"2018","journal-title":"Cell Transplant."},{"key":"ref_38","first-page":"4876","article-title":"Effects of hydrogen sulfide (H2S) on respiration control of state 3\/4 in mitochondria from bovine heart","volume":"11","author":"Su","year":"2012","journal-title":"Afr. J. Biotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/332462a0","article-title":"The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins","volume":"332","author":"Kozutsumi","year":"1988","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/sj.cdd.4401365","article-title":"Ischemia-induced neuronal cell death is mediated by the endoplasmic reticulum stress pathway involving CHOP","volume":"11","author":"Tajiri","year":"2004","journal-title":"Cell Death Differ."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3460","DOI":"10.1016\/j.bbamcr.2013.06.028","article-title":"ER stress-induced cell death mechanisms","volume":"1833","author":"Sano","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1096\/fj.12-218875","article-title":"Modulation of ER stress and apoptosis by endoplasmic reticulum calcium leak via translocon during unfolded protein response: Involvement of GRP78","volume":"27","author":"Hammadi","year":"2013","journal-title":"FASEB J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/sj.cdd.4401373","article-title":"Roles of CHOP\/GADD153 in endoplasmic reticulum stress","volume":"11","author":"Oyadomari","year":"2004","journal-title":"Cell Death Differ."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1186\/1475-2840-12-158","article-title":"Protein kinase RNA-like endoplasmic reticulum kinase (PERK) signaling pathway plays a major role in reactive oxygen species (ROS)-mediated endoplasmic reticulum stress-induced apoptosis in diabetic cardiomyopathy","volume":"12","author":"Liu","year":"2013","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.mam.2018.03.002","article-title":"ROS signaling and ER stress in cardiovascular disease","volume":"63","author":"Ochoa","year":"2018","journal-title":"Mol. Aspects Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s13046-019-1047-9","article-title":"CYT997(Lexibulin) induces apoptosis and autophagy through the activation of mutually reinforced ER stress and ROS in osteosarcoma","volume":"38","author":"Wang","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1038\/cdd.2012.74","article-title":"PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress","volume":"19","author":"Verfaillie","year":"2012","journal-title":"Cell Death Differ."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1186\/s13046-018-0987-9","article-title":"Isoalantolactone induces apoptosis through ROS-mediated ER stress and inhibition of STAT3 in prostate cancer cells","volume":"37","author":"Chen","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/sj.jcbfm.9600005","article-title":"Damage to the endoplasmic reticulum and activation of apoptotic machinery by oxidative stress in ischemic neurons","volume":"25","author":"Hayashi","year":"2005","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.redox.2018.02.019","article-title":"Ripk3 promotes ER stress-induced necroptosis in cardiac IR injury: A mechanism involving calcium overload\/XO\/ROS\/mPTP pathway","volume":"16","author":"Zhu","year":"2018","journal-title":"Redox Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/16\/3975\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:11:24Z","timestamp":1760188284000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/16\/3975"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,15]]},"references-count":50,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2019,8]]}},"alternative-id":["ijms20163975"],"URL":"https:\/\/doi.org\/10.3390\/ijms20163975","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,15]]}}}